The hard and soft tissues of the mouth are covered with microbial populations that contain bacteria with different metabolic capabilities. The Gram-positive bacteria within these microbial populations readily catabolize carbohydrates to produce acids which attack the hard tissues of the oral cavity, resulting in the formation of dental caries lesions or cavities. In contrast, the Gram-negative bacteria, especially the anaerobes readily metabolize various amino acids contained in salivary and, to lesser extent, other peptides and proteins in the oral cavity to form end-products which favor the formation of oral malodor and periodontitis. This process of peptide, protein and amino acid degradation by the mouth bacteria is referred to as oral bacterial putrefaction. The mixture of malodorous compounds produced by the Gram-negative anaerobic bacteria during putrefactive degradation of proteins, peptides and amino acids include hydrogen sulfide, methyl mercaptan, and dimethyl sulfide (formed from the sulfur containing amino acids cysteine, cystine and methionine); indole and skatole (formed during the metabolism of tryptophan); cadaverine and putrescine (produced from lysine and ornithine); and butyrate and valerate (produced from the metabolism of other amino acids). The production of these malodorous compounds in the oral cavity results in a condition commonly referred to as oral malodor. It is estimated that about 75% of all adults have some form of this condition.
Hydrogen sulfide, methyl mercaptan, butyrate and propionate are putrefaction end-products that also have cell and tissue altering non-inflammatory roles in the periodontitis process. Hydrogen sulfide and methylmercaptan are compounds particularly effective in facilitating the oral epithelium penetrability of toxins and other large molecular weight compounds produced by Gram-negative bacteria, and leading to the inflammation and tissue degradation characteristics of gingivitis and periodontitis. Gingivitis is a condition in which the gingiva is red, swollen and bleeding. If left untreated, gingivitis may develop into periodontitis, a condition characterized by destruction of the periodontium, including epithelial attachment loss, periodontal membrane and ligament destruction, and loss of gingiva and alveolar bone. Severe periodontitis resulting in deep periodontal pockets may ultimately result in tooth loss.
Adult periodontal disease is a widespread medical problem that is difficult to treat, especially in the middle-aged and elderly. It develops when bacteria indigenous to the oral cavity colonize gingival sulci, forming bacterial plaques in the absence of oral hygiene. Inflammation (gingivitis) develops and eventually spreads, causing tooth attachment loss (periodontitis). The diversity of the oral flora, the chronic nature of the disease, and the absence of a generally accepted animal or in vitro model, have made the molecular pathogenesis of this disease by bacteria difficult to study. Therapies for this disease have also been hampered by ignorance of the bacterial induction process. Current therapy requires that the dentist improve oral hygiene by debridement (scaling and root-planing) and repair tissue architecture using periodontal surgery as necessary. The patient must undertake regular toothbrushing and flossing. This therapy is expensive, time-consuming and unpredictable in its outcome.
Previous studies have largely otherwise focused on the use of germicidal agents to treat gingivitis-periodontitis and oral malodor. Recent findings have recognized that gingivitis-periodontitis and oral malodor arise from a common process, oral bacterial putrefaction.
Both gingivitis and periodontitis are inflammatory diseases caused by plaque formation on the teeth. Chronic periodontitis often leads to destruction of the tissues supporting the teeth. Plaque can be defined as a soft bacteria-containing coating on the surface of a tooth. When a tooth is not clean, plaque formation will commence and this will lead to gingivitis in the gingival area.
The inflammation of the gingiva leads to the formation of the gingival sulcus, and a gingival pocket is formed. Clear evidence that plaque is responsible for gingivitis was derived from the induction of experimental gingivitis (H. Loe et al., J. Periodontology 36: 177-187, 1965). Starting from a state of clinical gingival health, all participants developed gingivitis within 10 to 21 days after elimination of oral hygiene procedures. After reinstating plaque control, the gingiva returned to a normal condition within seven days.
Gingivits is characterizered by swelling and redness of the free gingival margin. Bleeding is caused by, for example, toothbrushing and gentle probing by a dentist. There is a loss in the connective tissue tone, which tends to open the gingival sulcus. The disease process may be combatted by either eliminating the plaque or by altering the environment by changing the composition of the plaque.
In order to colonize a surface, bacteria must be able to adhere to the surface in question. The mucous epithelium of the oral cavity is constantly renewed, so that bacteria adhering to the mucosal surface will tend to be sloughed off together with the outer layer of dead cells of the epithelium, thus preventing bacterial invasion of the living tissue underneath the dead epithelial cells. On the other hand, the dental surface constitutes a firm non-living base to which bacteria effectively adhere. The bacterial colonies on the dental surface (plaque), especially at the gingival margin and in the subgingival region, are not removed by any similar process, resulting in an antibacterial immune reaction from the surrounding tissue evident as a chronic inflammation of the gingival tissue. Under normal and healthy conditions this inflammatory reaction is mild, with a delicate balance being struck between colonizing bacteria and antibacterial effect.
Inflammation of the gingiva due to bacterial colonization of the dental surfaces is therefore an important initial stage of periodontitis. If the bacterial colonies (plaque) are not removed, accumulation of bacteria along the gingival margin or in the dento-gingival region will lead to increased gingival inflammation and destruction of the periodontal membrane possibly followed by bone resorption. Eventually a periodontal pocket develops in which more bacteria accumulate, resulting in increased inflammation and infection proper of the tissue so as to lead to a more pronounced degradation of the tooth-supporting tissue.
Wherever there is a plaque-coated surface, calcium ions can take part in chemical reactions, giving rise to formation of calculus. Calculus can be found on the tooth surface as supra-gingival or subgingival deposits. These deposits must be removed in order to maintain normal gingival conditions.
A characteristic of periodontal infection is that once bacteria/plaque have established themselves (i.e. infected) firmly in a periodontal pocket, the natural humoral defense mechanisms are not capable of dealing with the infection, and the plaque may turn into hard deposits, i.e. calculus.
Apart from the general inflammation caused by the presence of bacteria/plaque, the release of hydrolytic enzymes like hyaluronidase, desoxyribonuclease, collagenase and proteases probably contributes to the destruction of dental tissue.
The severity of tissue damage probably depends on the antigen/antibody reaction of the organism as well as the degree of retention of inflammatory products in the periodontal pockets. Accumulation of mediators of local inflammation accelerates the process. In most cases the process is slow, with immunoinfiltration of the gingival tissue and formation of granulation tissue which contains inflammatory cells. Occasionally, this slow progression is superseded by acute exacerbations with accumulation of inflammatory cells and release of lysosomal enzymes. Such exacerbations are probably due to changes in the bacterial flora.
Juvenile periodontitis differs from the above marginal periodontitis only by an early onset, and by often involving certain groups of teeth and being accompanied by a much lesser degree of plaque formation. It begins in late childhood, resulting in a pronounced loss of the teeth's supporting tissue, and it too is an infectious disease on a par with other periodontal diseases.
Current periodontal therapy is directed towards the removal of bacterial plaque and calculus deposits—subgingival and supragingival plaque. These goals are usually achieved by means of scaling and polishing, instruction in oral hygiene procedures, periodontal surgery where indicated and periodic maintenance.
Another option for treatment, which remains to be fully evaluated, is the possibility of disrupting the subgingival microflora in such a way that supragingival plaque control becomes less important. One potential approach to such a treatment is intensive intermittent disruption using local or systemic antimicrobial agents, examples of which are metronidazole, tetracycline and erythromycin. Such agents may also be used for irrigation of the periodontal pockets. The potential effect is based on the concept that alteration of the subgingival microflora at appropriate intervals may be sufficient to prevent the development of an ecosystem suitable to the reestablishment of pathogens in adequate levels for disease initiation. Another approach is bacterial substitution, replacing potential pathogens with bacteria which occupy the same ecological niche but have a reduced pathogenic potential.
Still another approach is the use of chemical agents which will alter plaque and subgingival microflora sufficiently to prevent gingivitis or the development of gingivitis into parodontitis.
A vast number of chemical agents have been evaluated as potential antiplaque/antigingivitis agents. The first generation agents are antibacterial agents with limited effectiveness. These agents are effective as antibacterials in vitro, but are either not retained intra-orally or they are rapidly released. Therefore, they inhibit the bacteria for a short period of time, after which time bacteria growth is resumed. Their clinical effect is limited unless the agents are used frequently, i.e. four to six times a day. This group includes topical antibiotics, oxygenating compounds, quaternary ammonium compounds, phenolic compounds, and sanguinarine. The second generation agents are effective not only in vitro but also in vivo, due to their retention and release kinetics. At present, chlorhexidine and chlorhexidine analogues are the primary second generation compounds, and stannous fluoride may also qualify as belonging to this group.
Penicillin, tetracycline, erythromycin, polymyxin B, kanamycin, metronidazole and spiromycin have been used for anti-plaque treatment. However, the potential for the development of bacterial resistance and hypersensitivity reactions should limit the use of antibiotics for plaque control purposes. In general, antibiotics may hold great promise for specific bacterial diseases in the oral cavity, but they appear to be inappropriate for the routine control of supragingival plaque and associated diseases.
Quaternary ammonium compounds are cationic surface agents which are capable of reducing surface tension, absorbing to negatively charged surfaces and disrupting membranes. Plaque reducing effects have been reported with benzethonium chloride and cetylpyridinium chloride at 0.1%, when used four times daily. Side effects with quaternary ammonium compounds have included both ulcerations and discomfort.
Phenolic compounds have a long history of use in the oral cavity as either a mouthwash or as throat lozenges. A commercial preparation (Listerine®) of thymol, eucalyptol, methyl salicylate, benzoic acid and boric acid has shown a certain plaque reducing effect as compared to a placebo. It is not clear whether the degree of plaque inhibition due to this agent is of long-term value in the prevention of periodontitis.
Sanguinarine, a benzophenanthradine alkaloid, has recently been reported to be potentially useful as a plaque control agent. Preliminary studies indicate that sanguinarine is capable of providing some reduction and prevention of plaque and gingivitis.
Chlorhexidine gluconate in 0.1-0.2% solutions and 1% gels have been shown to exert an effective plaque inhibiting and anti-gingivitis effect, when used short-term. A few long-term studies with chlorhexidine gluconate have also shown promising effects against plaque formation. The oral use of chlorhexidine has been associated with staining of the teeth and tongue and a bitter taste, and longer use often gives rise to alterations of the mucosa. Owing to the cationic nature of the compound, it is difficult to mask the taste by addition of flavoring agents without affecting the biological activity. Other agents such as alexidine and octenidine are structurally similar to chlorhexidine, and appear have a comparable effect.
In summary, treatment of gingivitis and periodontitis has mainly been prophylactic, emphasizing the importance of removing calculus and dental plaque and generally improving oral hygiene by mechanical means such as toothbrushing using fluoride-containing toothpastes etc., and using dental floss, toothpicks and the like. When necessary, surgical methods have been used in order to reduce the depth of the periodontal pockets. Systemic or topical antibacterial treatment with tetracyclin or the like has also been shown to have some effect, especially during acute infectious episodes, and finally, irrigating or rinsing the mouth with antiseptics such as chlorohexidine has been shown to exert a certain, if limited, effect, especially on gingivitis and plaque formation. However, none of these treatments are entirely satisfactory as they either require a high degree of patient compliance and/or do not possess a high degree of efficiency.
There is therefore a need to provide an effective method for promoting oral hygiene and treatment, either prophylactic or therapeutic treatment, of gingivitis, other periodontal problems and oral mal odor.